Back to Search
Start Over
Randomized placebo controlled trial evaluating the safety and efficacy of single low-dose intracoronary insulin-like growth factor following percutaneous coronary intervention in acute myocardial infarction (RESUS-AMI).
- Source :
-
American heart journal [Am Heart J] 2018 Jun; Vol. 200, pp. 110-117. Date of Electronic Publication: 2018 Apr 03. - Publication Year :
- 2018
-
Abstract
- Background: Residual and significant postinfarction left ventricular (LV) dysfunction, despite technically successful percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), remains an important clinical issue. In preclinical models, low-dose insulin-like growth factor 1 (IGF1) has potent cytoprotective and positive cardiac remodeling effects. We studied the safety and efficacy of immediate post-PCI low-dose intracoronary IGF1 infusion in STEMI patients.<br />Methods: Using a double-blind, placebo-controlled, multidose study design, we randomized 47 STEMI patients with significantly reduced (≤40%) LV ejection fraction (LVEF) after successful PCI to single intracoronary infusion of placebo (n = 15), 1.5 ng IGF1 (n = 16), or 15 ng IGF1 (n = 16). All received optimal medical therapy. Safety end points were freedom from hypoglycemia, hypotension, or significant arrhythmias within 1 hour of therapy. The primary efficacy end point was LVEF, and secondary end points were LV volumes, mass, stroke volume, and infarct size at 2-month follow-up, all assessed by magnetic resonance imaging. Treatment effects were estimated by analysis of covariance adjusted for baseline (24 hours) outcome.<br />Results: No significant differences in safety end points occurred between treatment groups out to 30 days (χ <superscript>2</superscript> test, P value = .77). There were no statistically significant differences in baseline (24 hours post STEMI) clinical characteristics or LVEF among groups. LVEF at 2 months, compared to baseline, increased in all groups, with no statistically significant differences related to treatment assignment. However, compared with placebo or 1.5 ng IGF1, treatment with 15 ng IGF1 was associated with a significant improvement in indexed LV end-diastolic volume (P = .018), LV mass (P = .004), and stroke volume (P = .016). Late gadolinium enhancement (±SD) at 2 months was lower in 15 ng IGF1 (34.5 ± 29.6 g) compared to placebo (49.1 ± 19.3 g) or 1.5 ng IGF1 (47.4 ± 22.4 g) treated patients, although the result was not statistically significant (P = .095).<br />Conclusions: In this pilot trial, low-dose IGF1, given after optimal mechanical reperfusion in STEMI, is safe but does not improve LVEF. However, there is a signal for a dose-dependent benefit on post-MI remodeling that may warrant further study.<br /> (Copyright © 2018. Published by Elsevier Inc.)
- Subjects :
- Cytoprotection drug effects
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Monitoring
Female
Growth Substances
Humans
Infusions, Intra-Arterial
Magnetic Resonance Imaging, Cine
Male
Middle Aged
Myocytes, Cardiac drug effects
Organ Size
Treatment Outcome
Ventricular Remodeling drug effects
Heart Ventricles diagnostic imaging
Heart Ventricles drug effects
Heart Ventricles pathology
Insulin-Like Growth Factor I administration & dosage
Percutaneous Coronary Intervention methods
ST Elevation Myocardial Infarction complications
ST Elevation Myocardial Infarction diagnosis
ST Elevation Myocardial Infarction therapy
Ventricular Dysfunction, Left diagnosis
Ventricular Dysfunction, Left physiopathology
Ventricular Dysfunction, Left prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6744
- Volume :
- 200
- Database :
- MEDLINE
- Journal :
- American heart journal
- Publication Type :
- Academic Journal
- Accession number :
- 29898838
- Full Text :
- https://doi.org/10.1016/j.ahj.2018.03.018